Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis

M. A. Nielsen, D. Køster, S. Greisen, A. Troldborg, K. Stengaard-Pedersen, P. Junker, K. Hørslev-Petersen, M. L. Hetland, M. Østergaard, M. Hvid, H. Leffler, T. W. Kragstrup, B. Deleuran

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Objective: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. Method: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. Results: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1β and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). Conclusions: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.

Originalspråkengelska
Sidor (från-till)33-41
TidskriftScandinavian Journal of Rheumatology
Volym52
Nummer1
Tidigt onlinedatum2022
DOI
StatusPublished - 2023

Ämnesklassifikation (UKÄ)

  • Reumatologi och inflammation

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